Interim Results From Phase Iii Trist Study Of Trovax In Renal Cancer
Oxford, UK – 22 September 2009: Oxford BioMedica (LSE: OXB), a leading gene therapy company, today announces interim results from its Phase III TRIST study of TroVax, a therapeutic cancer vaccine, in renal cancer. Although TroVax did not show a significant survival advantage compared to placebo in the total population (median survival of 20.1 months vs. 19.2 months; n = 732; p = 0.55), the survival advantage was significant in one of the predefined subsets, namely in patients with a good prognostic profile receiving interleukin-2 (IL-2) as standard of care (n = 100; p = 0.046). Additional exploratory analyses have confirmed that the anti-5T4 immune response induced by TroVax is associated with enhanced survival (p = 0.002)1, and have also identified haematological factors that were predictive of a more favourable immune response and greater survival benefit from TroVax. The Principal UK Investigator for the study, Professor Robert Hawkins of the Christie Hospital in Manchester, is presenting the TRIST results today at the joint 15th Congress of the European CanCer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO) in Berlin, Germany. The abstract (#17LBA) can be viewed at http://www.ecco-org.eu.
The interim analysis of the TRIST study reflects validated survival data censored to 13 March 2009. Of 732 evaluable patients, the total reported deaths were 165 in the TroVax arm and 166 in the placebo arm. For the majority of patients (>80%), the reported cause of death was disease progression. At the cut-off date, 401 patients (55%) were still on study with a median follow-up of 13 months. The interim analysis showed that:
• In the Intent to Treat population, estimated median survival for TroVax was 20.1 months versus 19.2 months for placebo (n = 732; p = 0.55). • In patients with a good prognostic profile receiving IL-2, TroVax reduced the risk of death by 46% compared to placebo (n = 100; hazard ratio (HR) = 0.54; p = 0.046). Median survival for the TroVax subset had not been reached versus 19.6 months for placebo. • The magnitude of the 5T4 antibody response to TroVax correlated with improved survival (p = 0.02)1, reinforcing similar observations in prior Phase II trials. • The anti-vector (MVA) response showed no analogous association, suggesting that survival is unrelated to patients’ general health status and immune competence. This further supports the assumption that the 5T4 antibody response is clinically active. • Baseline platelet levels were predictive of a more favourable immune response to TroVax. The immune response was significantly more favourable in patients with ‘normal’ baseline platelets (n = 232) compared to ‘abnormal’ (n = 57), (p = 0.002)2. • Lower baseline platelet and monocyte levels and higher baseline haemoglobin levels were associated with increased survival benefit for TroVax versus placebo. • In patients with ‘normal’ baseline levels of these three haematological parameters, TroVax showed a promising trend in overall survival and an indicative 27% reduction in the risk of death versus placebo (n = 368; HR =0.73). The hazard ratio attained in this subset was consistent with the targeted primary endpoint for the TRIST study. • TroVax was well tolerated alongside standard of care and did not alter the serious or non-serious adverse event profile compared to placebo. The most common (>20%) treatment-related adverse events were pyrexia, fatigue, weight loss and nausea.
TRIST (TroVax Renal Immunotherapy Survival Trial) is a randomised Phase III study comparing TroVax to placebo, when added to first line standard of care. The trial enrolled 733 patients with advanced or metastatic renal cancer that were classified as having a good or intermediate prognosis. Patients were randomised to one of three standards of care: IL-2, interferon-alpha or sunitinib. As previously reported, vaccinations were discontinued on 11 July 2008 based on the recommendation of the study’s independent Data Safety Monitoring Board, which concluded that the study would not meet its predefined primary endpoint of an improvement in overall survival.
Professor Hawkins commented on the TRIST interim analysis: “The results presented today demonstrate that TroVax has a good safety profile and potentially improves patient survival in certain subsets of renal cancer. Importantly, the magnitude of the 5T4 immune response appears to correlate with clinical activity. The identification of baseline factors that may be predictive of a more favourable response to TroVax provides an excellent opportunity to optimise the design of future studies. Although I am disappointed that the trial did not meet its primary endpoint, I believe that TroVax is still of potential benefit to patients with cancer and I hope further studies will be initiated with more refined target populations.”
John Dawson, Oxford BioMedica’s Chief Executive Officer, added: “We are encouraged by the positive findings from our detailed analyses of the TRIST data. With these results, we aim to progress discussions with prospective partners and the oncology community in order to initiate further trials of TroVax as soon as possible. We are grateful to the clinical investigators and patients that participated in the TRIST study, whose contribution has significantly advanced our understanding of TroVax and its potential as a safe and effective therapeutic cancer vaccine.”
1. Log of ratio of 5T4 antibody titre at week 10 to baseline 2. Ratio of MVA to 5T4 antibody fold increase at week 10
For further information, please contact: Oxford BioMedica plc: John Dawson, Chief Executive Officer Nick Woolf, Chief Business Officer Tel: +44 (0)1865 783 000 JPMorgan Cazenove Limited: James Mitford/ Gina Gibson Tel: +44 (0)20 7588 2828 Media/Financial Enquiries: Lisa Baderoon/ Mark Court/ Mary-Jane Elliott Buchanan Communications Tel: +44 (0)20 7466 5000 US Enquiries: Thomas Fechtner The Trout Group LLC Tel: (646) 378 2900
Notes to editors 1. Oxford BioMedica Oxford BioMedica (LSE: OXB) is a biopharmaceutical company developing innovative gene-based medicines and therapeutic vaccines that aim to improve the lives of patients with high unmet medical needs. The Company’s technology platform includes a highly efficient gene delivery system (LentiVector®), which has specific advantages for targeting diseases of the central nervous system and the eye; and a unique tumour antigen (5T4), which is an ideal target for anti-cancer therapy. Through in-house and collaborative research, Oxford BioMedica has a broad pipeline and its partners include sanofi-aventis, Sigma-Aldrich and Wyeth. Technology licensees include Biogen Idec, GlaxoSmithKline, Merck & Co and Pfizer. Further information is available at www.oxfordbiomedica.co.uk
2. TroVax® TroVax is Oxford BioMedica’s novel therapeutic cancer vaccine, which is designed specifically to stimulate an anti-cancer immune response and has potential application in most solid tumour types. TroVax targets the tumour antigen 5T4, which is broadly distributed throughout a wide range of solid tumours. The presence of 5T4 is correlated with poor prognosis. The product consists of a Modified Vaccinia Ankara vector, which delivers the gene for 5T4 and stimulates a patient’s body to produce an anti-5T4 immune response. This immune response destroys tumour cells carrying the 5T4 antigen.
3. Hazard Ratio The hazard ratio is a summary of the difference between two survival curves, representing the reduction in the risk of death on treatment compared to the control over the course of the study. A hazard ratio of one means that there is no difference in survival between the two groups. A hazard ratio of 0.5 means the relative risk of dying in the treatment group is half the risk of dying in the other group.
4. ECCO 15-34th ESMO Congress The ECCO 15-34th ESMO Congress will take place at the ICC Berlin – Internationales Congress Centrum, Messedamm 22, D-14055 Berlin, Germany (www.icc-berlin.de) from Sunday 20 September to Thursday 24 September 2009. This joint congress between ECCO (European CanCer Organisation) and ESMO (European Society for Medical Oncology) provides a unique European forum for presentations of cutting-edge research from experimental and clinical oncologists, epidemiologists and cancer nurses. Over 15,000 scientists, doctors, nurses, patients, carers and industry representatives are expected to attend.
INTERIM RESULTS FROM PHASE III TRIST STUDY OF TROVAX® IN RENAL CANCER<http://db.buchanan.uk.com/handlers/fileDownloadH.jsp?id=-4159350079204412791&messageSendId=2398110880572591318>
Posted: September 2009